The aim of this work is to provide a better understanding of the mechanism of the polymerization and depolymerization of sickle Hb. The kinetics and thermodynamcis of the polymerization of various Hbs will be studied. To elucidate the nature of nuceli, changes in molecular propperties of Hb S and mixtures of sickle and non-sickle Hbs during the pregelation period will be measured by a low angle laser light scattering photometer under various experimental conditions. The applicants will also prepare oligomers of Hb S which are cross-linked during the nucleation step and investigatae whether these cross-linked oligomers can act as nuclei. The role of hybrid Hbs formed from sickle and non-sickle Hbs will be studied. The applicant and co-workers recently succeeded in chemically connecting two unlike chains intramolecularly with corss-linking agents, one of which is bis (3,5 dibromosalicyl) fumarate. I will the nature of the interaction of Hb S, Hb X during polymerization. Our studies on the polymerization of sickle and non-sickle Hbs suggested that there are many types of interactions between non-sickle nonomeric Hb and nuclei formed from Hb S. The nature of these interactions will be studied.